Background: Previous studies have shown a strong correlation between fetal nasal bone hypoplasia and chromosomal anomaly; however, there is little knowledge on the associations of fetal nasal bone hypoplasia with chromosomal microdeletions and microduplications until now. Chromosomal microarray analysis (CMA) is a high-resolution molecular genetic tool that is effective to detect submicroscopic anomalies including chromosomal microdeletions and microduplications that cannot be detected by karyotyping. This study aimed to examine the performance of CMA for the prenatal diagnosis of nasal bone hypoplasia in the second and third trimesters.
Subjects and Methods: A total of 84 pregnant women in the second and third trimesters with fetal nasal bone hypoplasia, as revealed by ultrasound examinations, were enrolled, and all women underwent karyotyping and CMA with the Affymetrix CytoScan 750K GeneChip Platform. The subjects included 32 cases with fetal nasal bone hypoplasia alone and 52 cases with fetal nasal bone hypoplasia combined with other ultrasound abnormalities, and the prevalence of genomic abnormality was compared between these two groups.
Results: Karyotyping detected 21 cases of chromosomal anomaly in the 84 study subjects (21/84, 25%), including trisomy 21 (14 cases), trisomy 18 (3 cases), 46, del (4)(p16) karyotype (2 cases), 47, XYY syndrome (1 case) and 46, XY, del (5) (p15) karyotype (1 case). CMA detected additional four fetuses with pathogenic copy number variations (CNVs) and six fetuses with uncertain clinical significance (VOUS). No significant difference was detected in the prevalence of genomic abnormality in fetuses with nasal bone hypoplasia alone and in combination with other ultrasound abnormalities (13/32 vs 18/52; χ² = 0.31, P > 0.05). The pregnancy was terminated in 21 fetuses detected with chromosomal abnormality and 4 fetuses detected with pathogenic CNVs. Among the other six fetuses detected with VOUS, the parents chose to continue the pregnancy, and the newborns all had normal clinical phenotypes.
Conclusion: In addition to chromosomal abnormalities identified in 21 fetuses by karyotyping, CMA detected additional 10 fetuses with abnormal CNVs (10/84, 11.9%) in the study population. CMA is a promising powerful tool for prenatal diagnosis that may provide valuable data for the accurate assessment of fetal prognosis and the decision of pregnancy continuation during the prenatal clinical counseling.
Keywords: nasal bone hypoplasia, chromosomal microarray analysis, prenatal diagnosis, copy number variation